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Processing-Independent Quantitation of Chromogranin A in Plasma from Patients with Neuroendocrine Tumors and Small-Cell Lung Carcinomas
Abstract
Background: Most neuroendocrine tumors express chromogranin A (CgA). The posttranslational processing of neuroendocrine proteins such as CgA is often specific for the individual tumor. To cope with this variability and improve tumor diagnosis, we developed a processing-independent analysis (PIA) method to measure the total CgA product. Methods: For PIA, samples underwent trypsin treatment followed by measurement of CgA by the “CgA(340→)” assay, in which the antiserum binds an epitope starting at amino acid 340 of CgA and including amino acid residues located in the C-terminal direction. The diagnostic accuracy of the CgA PIA and 3 sequence-specific assays for CgA were evaluated on plasma samples from patients with neuroendocrine tumors and small-cell lung carcinomas. Furthermore, we investigated whether the CgA plasma concentrations correlated with the tumor burden. Results: Size-exclusion chromatography of plasma showed that CgA immunoreactivity mainly consisted of high–molecular-weight forms, indicating that neuroendocrine tumors may secrete large amounts of poorly processed CgA. Accordingly, trypsination of plasma from 54 patients with neuroendocrine tumors or small-cell lung carcinomas increased the CgA(340→) immunoreactivity up to 500-fold. Both the CgA(340→) assay and the PIA measured significantly higher plasma concentrations in patients with very extensive disease than in patients with less widespread disease. The diagnostic sensitivity was 0.91 when using the CgA(340→) assay and 0.82 using the CgA PIA. Conclusion: The CgA(340→) assay and CgA PIA are both useful for diagnosis of neuroendocrine tumors and small-cell lung carcinomas and both assays correlate with tumor burden.
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Diagnostic sensitivity and specificity of CgA depend on the assay type, analytic specificity and sensitivity of the antiserum employed.
“Furthermore, diagnostic sensitivity and specificity depend on the assay type, analytic specificity and sensitivity of the antiserum employed [14], as does the fact that the CgA protein is heavily processed to smaller fragments [14,18,19,20].”
From Limited Diagnostic Utility of Chromogranin A Measurements in Workup of Neuroendocrine Tumors (2020) · cites this paper as [14]
The Discussion states that diagnostic sensitivity varies with assay specificity, and the evaluation of diagnostic accuracy reports different sensitivities for the four CgA assays (page numbers unavailable). Materials and Methods describes the epitopes recognized by the antisera. The copy does not establish that diagnostic specificity depends on assay type or on the antiserum’s analytic sensitivity. (LLM, conf=0.85)
Experimental — accuracy not yet measuredCgA PIA has demonstrated high diagnostic accuracy compared to the CgA340-348 RIA and other CgA assays without trypsin cleavage prior to measurement.
“CgA PIA has demonstrated a high diagnostic accuracy (i.e., diagnostic sensitivity and specificity) compared to the CgA340-348 RIA and other CgA assays without trypsin cleavage prior to measurement [14,18].”
From Limited Diagnostic Utility of Chromogranin A Measurements in Workup of Neuroendocrine Tumors (2020) · cites this paper as [14]
Table 4A (Discussion; page unavailable) reports high diagnostic sensitivity for CgA PIA (0.82), exceeding two sequence-specific assays but below the CgA(340–348) RIA (0.91). The Discussion says both PIA and that RIA are sensitive tools and that determining which is superior requires a larger study. The cited passages do not establish comparative diagnostic specificity, so they support only part of the claimed diagnostic accuracy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredPlasma chromogranin A (CgA) concentrations are related to tumor burden in patients with neuroendocrine tumors (NETs).
“Plasma chromogranin A (CgA) is related to tumor burden and recommended in the follow-up of patients diagnosed with neuroendocrine tumors (NETs).”
From Limited Diagnostic Utility of Chromogranin A Measurements in Workup of Neuroendocrine Tumors (2020) · cites this paper as [14]
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Metadata
- Authors
- Børglum, T., Rehfeld, J. F., Drivsholm, L. B., & Hilsted, L.
- Affiliations
- University Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark
- Rigshospitalet (DK)
- Næstved Sygehus (DK)
- Corresponding author
- Hilsted, Linda
- Venue
- Clinical Chemistry
- Publisher
- Oxford University Press (OUP)
- Published
- 2007-03-01
- Volume
- 53
- Issue
- 3
- Pages
- 438-446
- ISSN
- 0009-9147 (ISSN-L)
- 1530-8561
- OpenAlex
- W2132895322
- Cited by
- 42
- References
- 41
- Citations by year
- 2024: 1 · 2023: 2 · 2021: 6 · 2020: 4 · 2019: 2 · 2017: 3 · 2016: 1 · 2015: 3 · 2014: 3 · 2013: 3 · 2012: 1
- FWCI
- 2.06
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Clinical Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Sundhed og Sygdom, Det Frie Forskningsråd
- Rigshospitalet
- Medical Research Council
- Topics
- Health Sciences › Medicine › Oncology › Neuroendocrine Tumor Research Advances
- Health Sciences › Medicine › Oncology › Neuroblastoma Research and Treatments
- Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
- Keywords
- chromogranin A, neuroendocrine tumors, small cell lung cancer, trypsinization, plasma biomarkers, tumor burden, diagnostic sensitivity
- MeSH terms
- Adrenal Gland Neoplasms, Adult, Aged, Diagnosis, Differential, Female, Gastrointestinal Neoplasms, Humans, Immunoassay, Lung Neoplasms, Male, Middle Aged, Pheochromocytoma, Plasma, Reference Values, Severity of Illness Index, Carcinoma, Small Cell, Neuroendocrine Tumors, Chromogranin A
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